71475-45-1

Upstream product

• 123-07-9 4-Ethylphenol 
• 105-39-5 chloroacetic acid ethyl ester 
• 64-17-5 ethanol 
• 3926-62-3 sodium monochloroacetic acid 
• 19277-91-9 sodium p-ethylphenolate 
• 105-36-2 ethyl bromoacetate 
• 623-73-4 diazoacetic acid ethyl ester 
• 51828-69-4 ethyl (4-acetylphenoxy)-acetate 
• 122-59-8 2-phenoxyacetic acid 

Downstream Products

• 24431-27-4 2-(4-ethylphenoxy)acetic acid 
• 113511-44-7 4-Ethyl-phenoxy-acethydroxamsaeure 
• 2015168-50-8 2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide 
• 2015168-50-8 2-(4-ethylphenoxy)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)acetamide 
• 167762-94-9 2-(4-ethylphenoxy)acetyl chloride 
• 1401223-20-8 2-(4-ethylphenoxy)-N-isopropyl-N-((3-pyridin-3-yl)-1,2,4-oxadiazol-5-yl)methylacetamide 
• 727365-14-2 2-(4-ethylphenoxy)-N-isopropyl-N-((3-phenyl-1,2,4-oxadiazol-5-yl)methyl)acetamide 
• 71475-47-3 N-(3-Diethylamino-propyl)-2-(4-ethyl-phenoxy)-acetamide 

Relevant academic research and scientific papers

Methyl 3-(3-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)-propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism

Previously, we reported a hypoxia-inducible factor (HIF)-1 inhibitor LW6 containing an (aryloxyacetylamino)benzoic acid moiety inhibits malate dehydrogenase 2 (MDH2) using a chemical biology approach. Structure-activity relationship studies on a series of (aryloxyacetylamino)benzoic acids identified selective MDH1, MDH2, and dual inhibitors, which were used to study the relationship between MDH enzyme activity and HIF-1 inhibition. We hypothesized that dual inhibition of MDH1 and MDH2 might be a powerful approach to target cancer metabolism and selected methyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propanamido)-benzoate (16c) as the most potent dual inhibitor. Kinetic studies revealed that compound 16c competitively inhibited MDH1 and MDH2. Compound 16c inhibited mitochondrial respiration and hypoxia-induced HIF-1α accumulation. In xenograft assays using HCT116 cells, compound 16c demonstrated significant in vivo antitumor efficacy. This finding provides concrete evidence that inhibition of both MDH1 and MDH2 may provide a valuable platform for developing novel therapeutics that target cancer metabolism and tumor growth.

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.

PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)

Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1α inhibitors

A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1α inhibitors. Among the compounds synthesized, carboranylphenoxyacetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1α accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 μM). Compound 16 suppressed hypoxia-induced HIF-1α accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1α mRNA.

Neurotrophic substituted pyrimidines

The present invention relates to a series of substituted pyrimidines, to pharmaceutical compositions which contain them, to methods for their preparation and to their use in therapy, particularly in the treatment of neurodegenerative or other neurological

Neurotrophic substituted pyrimidines

The present invention relates to novel derivatives of a series of substituted pyrimidines, to pharmaceutical compositions which contain them, to methods for their preparation and to their use in therapy, particularly in the treatment of neurodegenerative

Rapid defunctionalization of carbonyl group to methylene with polymethylhydrosiloxane-B(C6F5)3

The polymethylhydrosiloxane-B(C6F5)3 combination is found to be a versatile carbonyl defunctionalization system under mild and rapid conditions. For the first time, B(C6F5)3 has been used as a nonconventional Lewis acid catalyst to activate PMHS. Aromatic and aliphatic carbonyl compounds were effectively reduced to give the corresponding alkanes in high yields.

Organic reactions catalyzed by methylrhenium trioxide: Reactions of ethyl diazoacetate and organic azides

Methylrhenium trioxide (CH3ReO3 or MTO) catalyzes several classes of reactions of ethyl diazoacetate, EDA. It is the first high valent oxo complex for carbene transfer. Under mild conditions and in the absence of other substrates, EDA was converted to a 9:1 mixture of diethyl maleate and diethyl fumarate. In the presence of alcohols, α-alkoxy ethyl acetates were obtained in good yield. The yields dropped for the larger and more branched alcohols, the balance of material being diethyl maleate and fumarate. An electron-donating group in the para position of phenols favors the formation of α-phenoxy ethyl acetates. The use of EDA to form α-thio ethyl acetates and N-substituted glycine ethyl esters, on the other hand, is hardly affected by the size or structure of the parent thiol or amine, with all of these reactions proceeding in high yield. MTO-catalyzed cycloaddition reactions occur between EDA and aromatic imines, olefins, and carbonyl compounds. Three-membered ring products are formed: aziridines, cyclopropanes, and epoxides, respectively. The reactions favor the formation of trans products, and provide a convenient route for the preparation of aziridines. Intermediate carbenoid and nitrenoid species have been proposed. In the presence of an oxygen source such as an epoxide, ethyl diazoacetate and azibenzil are converted to an oxalic acid monoethyl ester and tobenzil; at the same time the epoxide was converted to an olefin. These results provide further support for the proposed intermediate, a cyclic species containing Re, O, and CHCO2Et (or, occasionally, CPhC(O)Ph)in a three-membered ring.

16-Phenoxy and 16-substituted phenoxy-prostatrienoic acid derivatives

Novel racemic and 8R-antimeric 16-phenoxy- and 16-(o, m or p)-substituted phenoxy derivatives of 9α, 11α,15-trihydroxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acids, which may be further substituted at C-15 by a methyl or ethyl group, the pharmaceutically acceptable, non-toxic lower alkyl esters and salts thereof and processes for the production of such compounds. dl 9α,11α,15α-trihydroxy-16-m-trifluoromethylphenoxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid and dl 9α,11α,15 -trihydroxy-15 -methyl-16-m-trifluoromethylphenoxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid are representative compounds of the class. These compounds possess prostaglandin-like activities and thus are useful in the treatment of mammals where prostaglandins are indicated. They are particularly useful as luteolytic agents in female mammals.